[Sleep apnea in urology. Influence of obstructive sleep apnea on erection and bladder function]. / Schlafapnoe in der Urologie. Auswirkungen von obstruktiver Schlafapnoe auf Erektion und Blasenfunktion.

Obstructive sleep apnea syndrome affects 4-5% of middle-aged men. A high percentage of these patients suffer from additional urological diseases such as erectile dysfunction, nocturia, overactive bladder, and urgency incontinence. Awareness of these correlations is crucial for diagnosis and treatment of affected patients to avoid unnecessary medical treatment and even prevent fatal cardiovascular events, which can be associated with obstructive sleep apnea.

Influence of differences in sensitivity of Spanish and German consumers to perceive androstenone on the acceptance of boar meat differing in skatole and androstenone concentrations.

The reactions of German (n=472) and Spanish (n=480) consumers of the European boar taint study to boar meat were evaluated according to their androstenone sensitivity. Consumers were checked with pure substance for their androstenone sensitivity. Eighteen per cent of the German and 31% of the Spanish participants were highly sensitive to androstenone, with a significantly higher proportion of women. For insensitive/mildly sensitive consumers, skatole level was the main determinant for the rating of flavour and odour of pork. For highly sensitive consumers, androstenone significantly influenced the rating of odour (Spain and Germany) and flavour (Germany) and is the predominant problem for that group, due to the high percentage of carcasses with high androstenone levels.

[Telomerase in lung cancer. Testing the activity of the "immortaligy enzyme" bronchial biopsies increases the diagnostic yield in cases of suspected peripheral bronchogenic carcinomas]. / Telomeraseaktivität beim Bronchialkarzinom. Der Nachweis des "Unsterblichkeitsenzyms" in Bürstenbiopsien erhöht die diagnostische Ausbeute bei Verdacht auf ein peripheres Karzinom.

The proliferative capability is time-limited in normal somatic cells by the shortening of their chromosomal ends, the telomeres (Hayflick limit). An important feature of malignant cells is their immortality. The probably most common mechanism of tumour cells to achieve unlimited replicability is the activation of the enzyme telomerase. The reverse transcriptase can compensate the loss of telomeres. Using a PCR-based TRAP assay we found telomerase activity in tumour biopsies, exsudates and bronchial washings in various thoracic malignancies. In 38 of 47 patients with suspected peripheral lung cancer eventually surgery or invasive procedures proved a malignancy. In fluoroscopically guided bronchial brushings from 25 of these 38 patients (66%) the TRAP assay revealed telomerase activity. There was a single false positive case (tuberculosis) and with a single exception, the simultaneously taken brushes of the contralateral lobes were all telomerase negative. In 23 patients (61%) tumour cells were found in the cytological examination. In 33 patients at least one marker was positive. Thus the combination of cytology and telomerase test in bronchial brush biopsies attained a diagnostic yield of 87%.

Effects of energy and purines in the diet on proliferation, differentiation, and apoptosis in the small intestine of the pig.

The effects of the energy and purine content in the diet on mucosal cell mitosis, function, and apoptosis in the small intestine of pigs were investigated in two experiments. In experiment I, three groups of five pigs were first fed a commercial diet that contained 9.1 MJ metabolizable energy (ME) per kilogram dry matter (DM) and 16.4% crude protein. It was followed by the experimental diets for 5 days each starting with an energy deficit (5.8 MJ ME/kg DM; 7% crude protein) followed by a high-energy diet with low purine content (14.1 MJ ME/kg DM; 13.6% crude protein; 460 mg purines/kg), or alternatively an isocaloric high-purine diet (2,160 mg purines/kg). During experimental periods, blood samples were drawn daily through catheters for insulin-like growth factor-I (IGF-I) determination. The animals were killed at the end of the corresponding feeding period and gut tissue samples were collected. In tissue samples, IGF-I and parameters for the characterization of mitosis (thymidine kinase [TK], proliferating-cell nuclear antigen [PCNA]) and differentiation (RNA content, alkaline phosphatase, sucrase) were measured. The degree of apoptosis was determined histologically. In experiment II, five pigs were fitted with simple T-cannula at the distal jejunum. They were fed the three experimental diets consecutively for 7 days each and sucrase and alkaline phosphatase were measured in digesta (four samples daily). IGF-I in blood but not in tissue clearly responded to the energy content of the diet with a decrease during the deficit and an increase in the two high-energy groups. However, purines had no additional effect on IGF-I. TK, PCNA, and gut weight showed an energy effect on mitosis, which was paralleled by increased peripheral IGF-I. Purines led to a further increase of mitosis, but IGF-I and gut weight were not increased. The degree of mitosis was correlated with higher activities of sucrase and alkaline phosphatase and also with the number of apoptotic cells. The enzyme activity increased from the deficit to the high-energy group and was further elevated due to purines. The results from experiment II also confirm these effects of energy and purines, because the activities of the enzymes in digesta decreased during energy deficit, but increased due to energy and in addition to purines.

[Depressed mood in the acute phase of first ischemic cerebral infarct]. / Depressive Verstimmung im Akutstadium nach erstmaligem ischämischen Hirninfarkt.

In the acute phase of cerebral ischemia, 55% of the patients showed signs of mild depression after a period of 5-9 days. The development and intensity of depressive symptoms correlated strongly with the grade of functional impairment. A statistically less significant relationship was established between the depressive symptoms and low social status, higher age, lower predisease intelligence and accompanying symptoms of anxiety. Independent of antidepressive therapy, after 4 weeks an improvement in the initially registered functional and intellectual impairment as well as the depressive symptoms (prevalence rate 23.3%) was recorded. None of these parameters correlated with each other in any way. In conclusion, we interpreted these depressive symptoms as the result of reactive coping strategies during the acute phase of cerebral ischemia. In contrast to this, the aspect of gender showed no significant relationship to the resulting depressive symptoms. Furthermore, lesion location, lesion volume, and cortical atrophy and cognitive impairment proved to have no influence on depressive symptoms. This suggests that primary organic factors are not the cause of depression in connection with the acute stroke period.

Fura-2 calcium signals in skeletal muscle fibres loaded with high concentrations of EGTA.

Fura-2 is one of the most frequently used fluorescent Ca indicator dyes; yet it has limitations in tracking large intracellular Ca transients due to its high affinity for Ca. Since high affinity is of advantage when small Ca changes are to be detected, we tried the application of Fura-2 in skeletal muscle fibres which had been loaded with 15 mM internal EGTA to eliminate contractile artifacts. Under these conditions, the free Ca transients are considerably reduced in amplitude and strong saturation of Fura-2 is avoided. Cut segments of isolated muscle fibres were voltage-clamped in a double vaseline gap set-up. In the presence of high internal EGTA, free Ca (as measured with the rapid metallochromic indicator antipyrylazo III) drops rapidly from one value to a lower quasi steady-state value at the end of a depolarizing voltage pulse. This property allowed inspection of the dissociation kinetics of Ca from Fura-2 in the myoplasmic environment. The dissociation rate constant koff in the fibre was determined from the time constant of the exponential decay of the Fura-2 signal as a function of the final level of free Ca. We obtained a value of 26 s-1 at the experimental temperature of 12 degrees C. Knowledge of koff in the cell is essential for reconstructing the time course of free Ca from indicator bound Ca and for estimating the time course of the rate of release from the sarcoplasmic reticulum. The described combination of high EGTA buffering with Fura-2 fluorescence recording may be particularly useful for the determination of Ca release in small muscle cells.

Binding proteins for cyclic and linear oligopeptides in plasma membranes and the cytosol of rat hepatocytes.

Using a cyclolinopeptide A analogue, the hydrophobic cyclic peptide c(-Ala-Lys-Pro-Phe-Phe-Ala-Lys-Pro-Phe-Phe-), termed CDP (cyclodecapeptide), as ligand in affinity chromatography, hepatocellular peptide binding proteins were isolated from the integral part of plasma membranes and the cytosol. The sequence of the isolated protein with MW of 50 kDa from the integral part of the plasma membrane fraction was identical to cytochrome P450 II C13 and cytochrome P450 II C22, whereas the sequence of the 54 kDa protein was identical to 3-hydroxyandrogen-UDP-glucuronosyltransferase. These proteins have also been described as binding proteins for bile acids. As shown in earlier studies, bile acids and CDP also compete for uptake into hepatocytes. In the cytosol, a further known bile acid binding protein, the glutathione-S-transferase (G-S-T) subunit Yb1, was isolated and sequenced as binding protein for CDP and also for a further cyclopeptide, the somatostatin analogue OO8, and a linear peptide with renin-inhibiting activity, EMD 55068. As shown in uptake studies using isolated basolateral plasma membrane vesicles, G-S-T was able to increase the uptake of EMD 51921, a linear peptide with renin-inhibiting potency, into the vesicles when the latter were preloaded with G-S-T. The binding of the substrate to the outside of the preloaded vesicles was not different than binding to unloaded vesicles. The maximal transport rate of the carrier-mediated/facilitated diffusion and the rate of permeation, however, were doubled in the presence of G-S-T, pointing to the involvement of intracellular binding proteins such as G-S-T in the unloading of the carrier protein and in the reduction of the free substrate concentration.

Hepatobiliary elimination of certain peptide-mimicking drugs: linear hydrophobic and hydrophilic renin-inhibitors and hydrophobic cyclopeptides.

Kinetic investigations on the hepatocellular uptake of certain peptide-mimicking drugs revealed that in most cases carrier-mediated mechanisms are responsible for their rapid extraction from portal blood. The driving forces for uptake, however, are unknown. Uptake is not dependent on the presence of sodium ions. The membrane potential or other energy sources may drive their uphill transport. Efforts to isolate the transport proteins involved in hepatocellular uptake using the Xenopus laevis oocyte system failed due to high unspecific binding of the peptides. Intracellular cytosolic and membrane-associated binding proteins, however, were isolated and sequenced. Uptake of certain of the drugs investigated is related to the uptake of bile acids. The recently cloned bile acid transporters ntcp and oatp are not the related transport systems. The carrier protein for these peptide-mimicking drugs has yet to be cloned. At the canalicular pole of the cell, excretion of two linear renin-inhibitors EMD 51,921 and CGP 38,560 is due to ATP-dependent transport mechanisms. MDR gene products seem to be involved in the elimination of the renin-inhibitor CGP 38,560, whereas the endogenous ATP-dependent transport system for the renin-inhibitor EMD 51,921 has not been identified.

The 60-kDa bumetanide-binding protein from rat liver membranes is a catalase.

A hepatic bumetanide-binding protein of molecular mass 60 kDa was isolated from rat liver sinusoidal plasma membranes after photoaffinity labelling with [3H]bumetanide. The protein was purified by non-equilibrium pH gel electrophoresis/two-dimensional gel electrophoresis. The amino acid sequences of two internal fragments share 67% and 89% similarity with rat liver catalase, which has a molecular mass of 59.758 kDa. With H2O2 as a substrate, the catalytic activity was measured in rat liver plasma membrane preparations. This activity was blocked by bumetanide and aminobumetanide. Polyclonal antibodies were raised against the purified 60-kDa membrane bumetanide-binding protein. The antibody anti-Bum-Ab 60 immunoprecipitated a 60-kDa protein from rat hepatocytes. Immunoblot analysis of SDS/PAGE and two-dimensional PAGE gels confirmed that the antibody was specific for the 60-kDa bumetanide-binding protein and cross-reacted with commercially available purified bovine liver catalase. Immunofluorescence showed the presence of the 60-kDa antigen in the plasma membrane of intact hepatocytes. Western-blot analysis revealed that the protein was present in rat kidney cortex homogenate but was lacking in hepatoma cells AS-30 D, Reuber H35 FAO and HPCT cells (clone 1E3), in spleen, and in ileum. These results indicate that a plasma-membrane-derived catalase binds bumetanide in rat liver.

Pattern of failure and survival in endobronchial laser resection. A matched pair study.

To evaluate the influence of endobronchial laser resection on survival and the pattern of failure in patients with bronchial malignancies, we investigated 75 patients prospectively. These patients had radiation therapy (mean external dose, 53.1 Gy) and endobronchial laser resection to treat an inoperable or recurrent bronchial carcinoma occluding a major airway. Complete recanalization was achieved in 36 percent, partial recanalization was achieved in 51 percent, and no recanalization was achieved in 13 percent. These 75 patients were matched retrospectively with a group of 75 patients who received external radiation therapy because of the same indications, but because of endobronchial compression of a major airway by the tumor, received no laser resection. The patients were matched for age, sex, TNM-status, histologic features, external radiation dose and fractionation, lung resection, cytotoxic therapy, and brachytherapy; they were treated in the same period. The incidence of terminal hemorrhage was four times higher in patients who received endobronchial laser resection (34.5 percent) compared with those who did not (7.7 percent). Successful laser reopening of a major airway influenced the pattern of failure: with full recanalization the cause of death in 23.3 percent of cases was respiratory failure and in 26.7 percent, terminal hemorrhage; whereas with no recanalization these figures were 56.3 percent and 18.8 percent, respectively. Laser resection did not influence overall survival, but in patients with full reopening of a bronchus, the time interval from treatment to death was prolonged by more than 4 months compared with those patients in whom recanalization failed. Comparing our observations on the immediate cause of death with reports in the literature, we conclude that the higher percentage of terminal hemorrhage in patients receiving endobronchial laser resection is not directly related to the treatment, but reflects different patterns of tumor growth with respect to mucosal destruction not covered by the TNM system.

The role of ultrasound assisted thoracoscopy in the diagnosis of pleural disease. Clinical experience in 687 cases.

Ultrasonic examination is an established method used to differentiate between solid and liquid structures in the pleural space. It can estimate the volume of a pleural effusion and demonstrate whether the effusion is associated with loculations or adhesions. It is complementary to thoracoscopy. In the diagnosis of pleural disease ultrasonic-assisted thoracoscopy should only be used when the less invasive methods of diagnosis such as pleural aspiration for cytological, bacteriological and chemical examinations and needle biopsy of the pleura have not yielded a diagnosis. Although thoracoscopy is a relatively invasive procedure, it has the advantages of speed and accuracy in the diagnosis of pleural disease. This procedure is not widely used as it requires specialized instruments and equipment and may be time-consuming. The latter disadvantage may be minimized by the use of prior pleural sonography. The ultrasonic examination will indicate the optimal point of entry of the thoracoscopy to avoid adhesions. In order to evaluate feasibility, complications and clinical results in ultrasonic-assisted thoracoscopy, we investigated 687 patients with pleural diseases from 1987 to 1990. As prior induction of a pneumothorax under X-ray control was not necessary, the 20-30 min required for this procedure was saved in all patients. Very few complications were attributable to ultrasonic-assisted thoracoscopy as it could normally be performed under local anesthesia. A macroscopic diagnosis was made in 80% of malignant diseases and 77% of inflammatory diseases in our total of 687 thoracoscopies. The diagnosis of a malignant pleural effusion was confirmed histologically and cytologically in 95% of those 190 patients in whom it was present.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pathophysiology of tricuspid insufficiency: analysis of the motion of the tricuspid valve annulus using 2-dimensional echocardiography]. / Zur Pathophysiologie der Trikuspidalinsuffizienz: Bewegungsanalyse des Trikuspidalanulus mittels zweidimensionaler Echokardiographie.

We investigated tricuspid annular motion in patients with pulmonary hypertension and in normal controls to determine the greatest minimal diameter and percentage shortening of the tricuspid annulus required for functional tricuspid regurgitation. 73 patients were studied by 2-dimensional echocardiography: a control group of 30 patients (group I); 43 patients had pulmonary hypertension, 9 of whom were still in sinus rhythm (group II), the other 34 patients had atrial fibrillation. 19 of these showed competent tricuspid valve with contrast echocardiography (group III), whereas the 15 remaining patients had functional tricuspid regurgitation (group IV). An analysis of shape and position changes of tricuspid annulus during the heart cycle was performed. The maximal diameter (mm/m2) in the apical 4 chamber view was in group I 17.5 +/- 1.4, in group II 20.7 +/- 3.2 (vs. group I p less than 0.05), in group III 19.0 +/- 3.4 (vs. group II NS) and in group IV 25.7 +/- 6.0 (vs. group III p less than 0.001). The values for the minimal annular diameter (mm/m2) were in group I 13.7 +/- 1.2, in group II 17.4 +/- 3.5 (vs. group I p less than 0.01), in group III 16.6 +/- 3.3 (vs. group II NS) and in group IV 23.6 +/- 5.7 (vs. group p less than 0.001). The percent decrease (%) in group I was 21.5 +/- 3.3, in group II 17.0 +/- 6.9 (vs. group I p less than 0.05), in group III 12.8 +/- 4.7 (vs. group II p less than 0.05) and in group IV 7.9 +/- 3.4 (vs. group III p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Determination of the size of the right atrium in patients with pulmonary hypertension using 2-dimensional echocardiography]. / Grössenbestimmung des rechten Vorhofes bei Patienten mit pulmonaler Hypertonie mittels zweidimensionaler Echokardiographie.

Normal values for right atrial area and tricuspid annular diameter and their percentage shortening measured from the two-dimensional echocardiographic four-chamber view are now available. In this study right atrial size of patients with pulmonary hypertension is evaluated and the results compared with the M-mode findings of the right ventricle in order to detect pulmonary hypertension. Hemodynamics and echocardiograms of 60 patients (mean age 57 +/- 10 years) with mitral stenosis III-IV NYHA and concomitant pulmonary hypertension were examined. 20 patients in group I with atrial fibrillation had additional functional tricuspid incompetence. Unlike the 20 patients in group II, who had atrial fibrillation, the remaining 20 in group III were still in sinus rhythm. The mean pulmonary artery pressure was 44.1 +/- 9.3 mmHg in group I, in group II 33.9 +/- 6.3 mmHg (grp. I vs. grp. II p less than 0.001) and in group III 33.2 +/- 7.1 mmHg (grp. II vs. grp. III ns). The end-systolic index of the right atrial area in group I was 19.6 +/- 5.7 cm2/m2 and thus significantly greater than in group II with 10.6 +/- 2.3 cm2/m2 (p less than 0.001) and in group III with 9.1 +/- 2.5 cm2/m2 (p less than 0.001). The maximal diameter of the tricuspid annulus measured 24.6 +/- 5.5 mm/m2 in group I, 18.9 +/- 3.5 mm/m2 in group II (grp. I vs. grp. II p less than 0.001) and 20.2 +/- 2.2 mm/m2 in group II (grp. I vs. grp. II p less than 0.001) and 20.2 +/- 2.2 mm/m2 in group III.(ABSTRACT TRUNCATED AT 250 WORDS)